Since most conventional gene therapeutics for cancer are injected into a body through local administration, there is a limit of decreasing accessibility with respect to metastatic cancer spreading all over the body. Therefore, in the cases of diseases imperceptibly spreading all over the body, for example, metastatic cancer, although such diseases have been generally excluded from gene therapies until now, it is necessary to develop products capable of systemic administration to expand the gene therapy market.
As adenoviruses have become popular as gene transfer vectors due to various advantages, they are being increasingly used for cancer gene therapy, and used most frequently in patient clinical trials. Particularly, oncolytic adenoviruses capable of killing only cancer cells by being selectively proliferated only in the cancer cells can not only exhibit a therapeutic effect in primary infected cells, but also considerably increase a cancer therapeutic effect since the therapeutic effect can keep spreading like a domino effect due to a series of infections of surrounding tumor cells by a proliferating virus and killing of cancer cells. Meanwhile, when a therapeutic gene is loaded in an oncolytic adenovirus, a therapeutic gene is limitedly expressed only in cancer cells with high efficiency, and thus the therapeutic effect can be synergistically improved. In addition, since the proliferation of oncolytic adenoviruses in peripheral normal cells is inhibited, killing of cells does not occur, and thus safety is high. For this reason, the therapeutic gene-loaded adenoviruses have attracted attention as the next generation anticancer therapeutics.
However, in systemic administration, the virus-based gene therapeutics have limitations of fast removal of viruses caused by immune cells in the blood, a very small amount of the therapeutics delivered to target tumor tissue, and hepatotoxicity caused by accumulating a large amount of the therapeutics. In addition, in repeated administration, since a high concentration of neutralizing antibodies is formed, a therapeutic effect caused by the repeated administration is considerably reduced. Because of these reasons, all currently-developed oncolytic adenoviruses used in cancer treatment are locally administered. Therefore, it is necessary to develop novel and innovative methods that allow systemic administration and effectively deliver adenoviruses to a target such as tumor cells.
As one of the novel methods, a method for treating cancer by delivering the DNA of an oncolytic adenovirus to target tumor cells, instead of using the oncolytic adenovirus itself as a therapeutic, has been suggested. To this end, it is necessary to develop a method for more safely and efficiently delivering adenovirus DNA to tumor cells in the human body.
Throughout this specification, numerous papers and patent documents are provided as references and cited references thereof are shown. The disclosure of the cited papers and patent literatures are incorporated herein by reference in their entirety, and thus the level of the technological field including the present application and the scope of the present application are more fully described.